Abstract Chikungunya virus (CHIKV), an alphavirus in the Togaviridae family, is an important and dangerous viral pathogen that has spread around the world in recent years. CHIKV causes chikungunya fever and severe arthralgia that may persist for several months. Like Dengue Virus (DENV), CHIKV is also an arthropod-borne virus (arbovirus). Currently, no licensed vaccine or drug is available for human use for Chikungunya virus. We have recently developed a novel technology that is based on rational, computer-aided gene design, termed Synthetic Attenuated Virus Engineering (SAVE), to attenuate plus and minus strand RNA viruses (poliovirus, influenza virus dengue virus) by recoding their their genomes to introduce unfavored codon pairs. Those codon pair deoptimized viruses were all successfully attenuated both in tissue culture and in an animal model. Here, we propose to extend the SAVE approach to this emerging and dangerous viral pathogen, Chikungunya virus, to pursue the isolation of an attenuated viral strain. With the aid of computers and specifically tailored algorithms we will recode the genome of CHIKV such that it will contain large segments (encoding either the proteins nsP4, E2, E1) of codon pairs dis-favored in mammals. Based on our previous studies we expect that these recoded CHIK viruses will be similarly attenuated and will serve as possible live vaccine candidates